Diabetic autonomic neuropathy is a heterogenous syndrome with diffuse manifestations affecting many organ systems. Chronic diarrhea, gastroparesis, urinary retention, impotence and hypoglycemia unawareness are major clinical problems for patients with this condition. Postural hypotension, the focus of the present research proposal, is the classical feature of this disorder, yet the alteration in adrenergic physiology is poorly understood. Some patients have low circulating norepinephrine (NE) levels and a blunted NE response to postural stress whereas others exhibit normal or even high plasma NE and an exaggerated response to the asumption of an upright posture. Steady state plasma NE, however, provides only a crude index of NE secretion by sympathetic neurons, since factors affecting sympathetic neuronal reuptake and local metabolism may also be important determinants of circulating NE concentrations. For this reason, we have developed isotope tracer kinetic analysis techniques for estimating NE production and secretion in human subjects. The objective of the proposed research is to use these techniques to study NE metabolism in patients with postural hypotension secondary to diabetic autonomic neuropathy.